This Conte Center for the Neuroscience of Mental Disorders (CCNMD) offers a highly interactive scientific environment that integrates the basic and clinical research activities of multiple investigators from the University of Pittsburgh's Schools of Medicine and Arts and Sciences and the adjacent Carnegie Mellon University. Collectively, the CCNMD represents a broad array of expertise spanning molecular, systems, cognitive, computational and clinical neuroscience that provides complementary approaches to testing the central hypothesis that a distinctive pattern of molecular alterations in subpopulations of GABA neurons (pathology) gives rise to conserved disturbances in cortical network oscillations (pathophysiology) that underlie the core information processing deficits (clinical syndrome) of schizophrenia. The proposed 5 projects, supported by Administrative, Clinical Services and Diagnostics, and Statistics and Data Management Cores, examine 1) molecular abnormalities in schizophrenia in distinct subsets of cortical GABA neurons thought to generate oscillatory activity (Project 1-Lewis); 2) integrated computational, electrophysiological and anatomical approaches to determine the relationship between cell type-specific cortical GABA neurotransmission and oscillations in vitro (Project 2-Ermentrout); 3) the role of GABA neurotransmission in cortical oscillations elicited by tasks that tap in non-human primates the same information processing domains that are altered in schizophrenia (Project 3-Olson); 4) specific types of information processing disturbances in schizophrenia that are linked to altered activation of, and impaired network oscillations in, certain cortical regions (Project 4-Phillips); and 5) the development of new PET imaging tools for studying the function of human cortical GABA neurons in vivo (Project 5-Mathis). The synergism and bi-directional interactions of these projects facilitates a translational approach to schizophrenia research directing at identifying pathophysiology-based targets for novel therapeutic interventions and developing biomarkers of the pathophysiology that can be used to monitor the efficacy of such interventions. Thus, the proposed Center is a multi-disciplinary effort directed at testing a mechanistic hypothesis in order to improve our understanding of a core component of the disease process of schizophrenia. In addition, the Center provides 1) a rich environment for training and career development in which individuals can become involved in studies that bring the methods and knowledge base of basic neuroscience to address critical questions in clinical schizophrenia research, and 2) a mechanism for disseminating the importance of, and the knowledge gained from, translational studies of schizophrenia to the broader scientific and lay communities.